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dc.contributor.authorPapareddy, Praveenen
dc.contributor.authorKalle, Martinaen
dc.contributor.authorMorgelin, Matthiasen
dc.contributor.authorSchmidtchen, Arturen
dc.contributor.authorMalmsten, Martinen
dc.contributor.authorSingh, Shalinien
dc.identifier.citationPapareddy, P., Kalle, M., Singh, S., Mörgelinc, M., Schmidtchen, A., & Malmsten, M. (2014). An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1838(5), 1225-1234.en
dc.description.abstractHost defense peptides are key components of the innate immune system, providing multi-facetted responses to invading pathogens. Here, we describe that the peptide GKS26 (GKSRIQRLNILNAKFAFNLYRVLKDQ), corresponding to the A domain of heparin cofactor II (HCII), ameliorates experimental septic shock. The peptide displays antimicrobial effects through direct membrane disruption, also at physiological salt concentration and in the presence of plasma and serum. Biophysical investigations of model lipid membranes showed the antimicrobial action of GKS26 to be mirrored by peptide incorporation into, and disordering of, bacterial lipid membranes. GKS26 furthermore binds extensively to bacterial lipopolysaccharide (LPS), as well as its endotoxic lipid A moiety, and displays potent anti-inflammatory effects, both in vitro and in vivo. Thus, for mice challenged with ip injection of LPS, GKS26 suppresses pro-inflammatory cytokines, reduces vascular leakage and infiltration in lung tissue, and normalizes coagulation. Together, these findings suggest that GKS26 may be of interest for further investigations as therapeutic against severe infections and septic shock.en
dc.format.extent10 p.en
dc.relation.ispartofseriesBiochimica et biophysica acta (BBA) - biomembranesen
dc.rights© 2014 Elsevier B.V. This is the author created version of a work that has been peer reviewed and accepted for publication by Biochimica et Biophysica Acta (BBA) - Biomembranes, Elsevier B.V. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [].en
dc.titleAn antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivoen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.description.versionAccepted versionen
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Appears in Collections:LKCMedicine Journal Articles

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